The overall goals of the Immunology Program are to support research activities related to the immune response to cancer, and the development and activation of hematopoietic cells. These research foci are supported by an outstanding basic science program to understand the biology of the immune system and immune responses, and by a strong and highly collaborative Immunotherapy translational program, which develops clinical trials based on this knowledge. The guiding principal of the Program is that effective manipulation of the immune response to cancer must be based in a broad understanding of how the immune system is regulated. Strategies to control hematopoietic malignancies are also rooted in an understanding of the mechanisms that regulate the activation and differentiation of normal cells in hematopoietic lineages. Investigators in the Immunology Program have provided new understanding of the development and regulation of immune responses, and have been at the forefront of national and international efforts to establish a strong scientific basis for cancer immunotherapy. This Program is divided into 3 themes: 1) Identification of Tumor Antigens; 2) Immune Responses in Cancer Development and Control; and 3) Hematopoietic Cell Development, Activation, and Survival. Each comprises a critical mass of investigators who are exploring ways to apply basic knowledge about the function of the immune system to the control of cancer and to improved modalities for the treatment of cancer patients. The Immunology Program is currently composed of 29 members in 7 departments. Since the last renewal, this Program has added 16 new members who have provided additional strength in key areas and enhanced cancer focus within the Program, leading in turn to the establishment of significant new cancer-related initiatives. The members of this Program have published 463 papers since the last renewal, of which 19% are intraprogrammatic and 21% are inter-programmatic. In the current budget year, the members of this Program are responsible for $1.5M in direct costs from NCI-funded awards, out of a peer reviewed direct cost funding total of $14M. The enhanced cancer focus, collaborative interactions, and new initiatives engendered during the current funding period provide a strong basis for development and clinical implementation of strategies to improve immunity to solid tumors such as melanoma and ovarian carcinoma; improved understanding of the basis for Helicobacter pylori-induced gastric solid tumors; and improved therapeutic approaches to lymphoid malignancies.